Light-related diseases of phototoxicity, caused by exposures to light in the presence of endogenous or exogenous photosensitizers, are medical problems not well understood at the cellular level. The broad aims of this proposal are to reveal the mechanisms by which visible light leads to modification of cell membranes in the presence of photosensitizers. Among the sensitizers to be employed are a number of FDA-approved colorants, drugs, optical probes and dyes. Giant axons from lobsters will be sensitized by the addition of sensitizers to the external bathing medium and exposed to visible light from a xenon arc lamp. Sheep erthrocytes will be similarly exposed and illuminated by a fluorescent lamp. Axon properties will be studied in a double sucrose-gap voltage-clamp technique. The effectiveness of any sensitizer for block of sodium or potassium channels will be quantified by a relative effectiveness assay which is analogous to a quantum yield. The modification of erythrocyte membranes will be quantified by a percent photohemolysis. Hypothesis concerning the lipid location of sensitizers and the nature of the initially modified protein moieties will be tested.